The blood levels of lipoproteins are used as an indicator of risk of atherosclerosis and familial hypercholesterolemia. Little is known, however, concerning the regulatory mechanisms involved in the synthesis and secretion of lipoproteins. These events are readily studied in the immature cockerel since administration of estrogen results in large increases in lipoproteins. We have demonstrated that one lipoprotein, apo-VLDL-II is primarily regulated by hormones at the level of transcription. The purpose of the present investigation is to isolate the mRNA for apo-VLDL-II, prepare a cDNA probe, and use this to study the rate of specific mRNA transcription in a variety of physiological and pharmacological states. The cDNA will also be used to isolate a structural gene clone using recombinant DNA technology. The structural gene clone will be used in turn, to isolate the natural gene from a chicken gene library. Following amplification, the natural gene will be analyzed with respect to its structural organization and the 5' and 3' flanking regions will be sequenced. This information will be compared with such results already obtained for two other chicken genes regulated by estrogen in the oviduct, ovalbumin, and ovomucoid. A major question is why estrogen only regulates apo-VLDL-II in liver but ovalbumin and ovomucoid in oviduct and vice-versa. Finally, the natural gene clone will be used to study mRNA processing and whether splicing events are hormonally regulated. The results obtained should help in elucidating the precise mechanisms by which hormones regulate lipoprotein metabolism.